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The Obesogen Hypothesis and the Obesity Epidemic

Everyone knows we are in the middle of an obesity epidemic both in the USA and across the globe. The question of the day is, what really causes obesity? If that were known, then both prevention and intervention strategies could be put in place to reduce the incidence of obesity and its comorbid diseases and dysfunctions.

The focus of much of the medical and pharmaceutical communities is on reducing weight in obese subjects. So how effective are all the weight loss efforts? We all know the answer to this question from our own experience. Since there is a new “diet” every week, it is obvious that losing weight is a very difficult process with very few efficacious drugs. The other half of the equation is that once one loses weight, it is a constant struggle to keep it off. I personally have lost the same 15 pounds over 30 times --and many people have the same story.

Biologically different?

According to many, the reason for obesity is simple: overeating on a susceptible genetic background. Genetic differences result in individual differences in weight gain. However after 20 years of research only a few genes have been identified, and all together they can only account for less than 20% of weight gain. Certainly some people overeat, but even in the presence of the same food, not all people overeat and some who overeat do not always gain weight. Lean individuals eat primarily to sustain fitness and tend to stop eating when they perceive they are full, even when food is bountiful. Obese people tend to eat more high-fat and high-sugar foods and continue to eat even when they are not hungry, suggesting addiction. Are they biologically different?

While it is not entirely clear whether the psychological and physiological characteristics of the obese are a cause, or consequence, of weight gain, it appears likely that there are common underlying changes in behavioral circuitry predisposing individuals to gain weight.

Perturbations during development

To address this question, let’s start with what we know about obesity. It results from dysfunction of one or more of the highly integrated and coordinated endocrine systems that control eating behavior, fat cell development and number, and metabolic activity. Thus any dysfunction in the control of brain, adipose tissue, liver, skeletal muscle or gastrointestinal tract function could theoretically upset the delicate endocrine balance, resulting in susceptibility to gain weight. In addition it is now clear that susceptibility to many diseases, including obesity, may start during development (in utero and early life). A perturbation while the tissues and organs are developing could lead to increased susceptibility to weight gain.

What might be the source of that perturbation? All aspects of the integrated endocrine system are subject to disruption by environmental chemicals with endocrine properties, e.g. endocrine disruptors. Endocrine disruptors by definition are environmental chemicals that act via altering endocrine pathways. When these pathways are altered during development, their effects are “programmed” and thus remain throughout life.

Lifelong susceptibility

This discussion points us to the new field of “obesogens.” Obesogens are endocrine disruptors that act on some part of the endocrine system controlling weight gain -- adipose tissue, gastrointestinal tract, brain, skeletal muscle, liver or pancreas -- to disrupt normal function, leading to increased weight gain. Obesogens can act at any of the tissues important in weight control and indeed may have multiple sites of action. The obesogen hypothesis states that exposure to certain chemicals during development will affect tissue and organ development, leading to increased susceptibility to gain weight throughout life: these chemicals can alter the set-point for gaining. Thus, developmental exposure may “program” the endocrine system controlling weight gain and metabolism so one might gain weight more easily, or be required to exercise more to lose weight. Or they might alter food preferences and cravings. As a lifelong result, additional obesogen exposures along with exposure to high fat and sugary foods and lack of exercise can add to the susceptibility, potentially leading to obesity, diabetes and even to metabolic syndrome.

Although the study of obesogens is less than 10 years old, about 15 chemicals and classes of chemicals have already been shown to result in weight gain from developmental exposures in animal models. These include bisphenol A, tributyl tin, some flame retardants (PBDEs), perchlorinated biphenyls (PCBs), and some organochlorine pesticides (, DDT metabolites, oxychlordane, parathion, chlorpyrifos), triflumizole ( fungicide), high fructose corn syrup, nicotine, benzo(a)pyrene, some phthalates, some surfactants (PFOAs), diethylstilbestrol and genistein -- and the list grows monthly.

There are currently only a few human studies examining developmental exposures and subsequent weight gain, but these studies suggest that the hypothesis developed in animal models may be relevant also to humans.

How important are obesogens to the current obesity crisis? At this point it is unclear; more research is needed to identify all the obesogens, to determine their sites of action in animal models, and to then examine them in human populations.

Nonetheless, if the obesogen hypothesis is true, we will have identified a time period when the sensitivity to develop obesity occurs (development) and some chemicals (obesogens) that might play a role the sensitivity or susceptibility to developing obesity. This will then lead to important prevention and intervention strategies which may be much more effective than the current pharmaceuticals which only act after the obesity occurs. Prevention is the most effective approach.

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*The opinions expressed do not necessarily reflect those of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the US Government.

Comments

Sylvia Richey said ..

All perfumed products contain deadly chemicals. If a personal care product such as shampoo, hand soap, creams, lotions, aftershave etc. lack the words on the labels, fragrance free or perfume free, they contain deadly chemicals that in the laboratory carry warnings like "Do not breathe the fumes," "Do not allow to touch the skin or eyes, "Do not flush to the sewer." Safe cleaning agents are either edible,or are marked "Free Clear," or Perfume Free. Why are people not being warned that they are making themselves and others sick by not using Perfume Free Products? Even the baby products contain harmful chemicals. How can we expect people to be well in such a climate?